In vitro and in vivo therapeutic potentials of the liposomes for hepatocellular carcinoma were improved via the anti-angiogenesis strategy and comprehensive tumor microenvironment remodeling, including HIF-1α-VEGF downregulation, depletion of cancer-associated fibroblasts, and inhibition of M2-type tumor-associated macrophage infiltration in desmoplastic tumor. The gene discussed is VEGFA; the disease is neoplasm.